Suicide is a leading cause of death among U.S. Veterans. Therefore, understanding the etiological basis for the risk of suicide is of dire importance to our Veteran population. Stress i a crucial factor in risk of suicide. Specifically for Veterans, exposure to traumatic environmental events during combat, military service, or post- deployment stressful situations related to readjustment to civilian life are key contributors to the increase risk of suicide. These stressors can affect the diathesis for suicidal acts and can serve as triggers or precipitants of suicidal acts. Biological markers or stable behavioral traits for suicide risk factors likely interact in a complex manner that might benefit from approaches that can examine gene by environment interactions. Epigenetics is the bridge, connecting environment with genetics, by mediating the influence of environmental factors such as stress in altered regulation of gene expression related to suicide. We will investigate DNA methylation patterns associated with suicide risk in Veterans undergoing psychiatric treatment at the JJP VAMC using a genome- scale approach. Additionally, through subsequent follow-up studies, we will assess how DNA methylation patterns are altered following treatment. Such a longitudinal study is unprecedented and provides an opportunity to identify biological markers of suicide risk and treatment response. Moreover, the role of the inflammatory response in the stress diathesis in suicide risk will also be investigated in these studies. Together the epigenetic and inflammatory markers of suicide risk and treatment will identify objective measures that we can use in clinical settings to identif Veterans at risk of suicide and to determine the efficacy of treatment course and response.